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@Dr. Leo Galland : 我是临床医生，也是转化型临床医生，致力于将基础科学研究应用于临床实践。我研究肠道微生物组、营养、身心连接和环境健康对疾病的影响已有40年。我发现，许多科学知识并未应用于常规医学实践，例如饮食模式对健康和疾病的重大影响，以及肠道微生物组在其中的作用。我研究了肠道通透性（leaky gut）的概念，以及肠道微生物组与新陈代谢、基因和免疫系统的相互作用。肠道微生物组产生的丁酸盐对表观遗传学有直接影响，它是一种组蛋白去乙酰化酶抑制剂，影响基因表达。益生菌的菌株非常重要，有些益生菌可以改变整个系统的动态，创造空间让其他微生物生长，我称之为“亚历山大菌”。布拉迪酵母菌和枯草芽孢杆菌7092菌株是“亚历山大菌”的例子。人们正在研究如何保护益生菌，使其在肠道的特定部位释放，以及如何利用靶向噬菌体疗法来改善肠道微生物组。抑制胃酸的药物会对肠道微生物组产生不利影响，胃酸不足也可能导致胃肠问题。对于酸敏感的人，控制症状的方法有很多，并不一定要抑制胃酸。我致力于帮助患者摆脱长期抑制胃酸的药物治疗，并采用营养方法来治疗疾病。

Leo Galland博士是一位内科医生，也是《过敏解决方案》一书的作者。Galland博士的研究生涯长达四十年，专注于将基础科学研究转化为临床实践，特别关注肠道微生物组、营养、身心连接以及环境健康对疾病的影响。

肠道微生物组：远不止于消化

Galland博士指出，许多重要的科学发现并未被常规医学实践所广泛应用。例如，饮食模式对疾病的严重程度有着显著的影响。在疫情期间的研究表明，患者在感染前一年的饮食习惯与COVID-19的严重程度密切相关。这并非仅仅是饮食本身的作用，而是饮食如何通过影响肠道微生物组来影响人体对疾病的反应。

他深入研究了“肠漏”（leaky gut）的概念，以及肠道微生物组与人体新陈代谢、基因表达和免疫系统之间的复杂相互作用。值得注意的是，人体三分之二的免疫细胞都位于小肠内壁，它们在肠道中“训练”，并影响全身免疫反应。

丁酸盐：表观遗传学的关键

Galland博士特别强调了肠道微生物组产生的丁酸盐（butyrate）的重要性。丁酸盐是一种挥发性短链脂肪酸，它不仅为大肠细胞提供能量，还具有抗炎和抗癌作用，并促进细胞修复。更重要的是，丁酸盐直接影响表观遗传学，它是一种组蛋白去乙酰化酶抑制剂，能够调节基因表达，例如在脑损伤修复中发挥关键作用。

益生菌与“亚历山大菌”

关于益生菌，Galland博士强调了菌株的重要性，并非所有益生菌都具有相同的效果。他提出了“亚历山大菌”的概念，指的是那些能够改变肠道微生物组整体动态，为其他有益菌创造生长空间的益生菌。布拉迪酵母菌（Saccharomyces boulardii）和枯草芽孢杆菌7092菌株就是这类“亚历山大菌”的例子。

靶向噬菌体疗法与益生菌递送

目前，研究人员正在探索如何保护益生菌，使其在肠道的特定部位释放，以最大限度地发挥其作用。靶向噬菌体疗法也展现出巨大的潜力，它可以特异性地清除有害菌，例如艰难梭菌（C. diff），为有益菌的生长创造条件。

胃酸与肠道健康

Galland博士还指出，长期使用抑制胃酸的药物会对肠道微生物组产生不利影响，增加感染风险。他强调，胃酸不足也可能导致胃肠问题，对于酸敏感的人群，控制症状的方法有很多，并不一定需要抑制胃酸。

功能医学：关注整体健康

Galland博士的研究成果为功能医学提供了重要的理论基础。功能医学关注个体差异和整体健康，而不是仅仅关注疾病本身。他致力于帮助患者摆脱依赖药物治疗的模式，并采用营养方法来治疗疾病。

结语

Galland博士的对话涉及肠道健康的重要性，以及饮食、营养和生活方式对整体健康的影响。他的研究为治疗慢性疾病提供了新的思路和方法， 强调了将基础科学研究应用于临床实践的重要性，以及关注个体差异和整体健康的重要性。 通过调节肠道微生物组， 可以改善免疫系统功能，治疗炎症，并最终提升整体健康水平。

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01:25 我在职业生涯早期就意识到，我的医学训练中提供的工具无法解决许多问题，所以我开始寻找问题的根源并寻求创新解决方案。

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02:09 我研究了科学文献，并将研究成果应用于我的临床实践，发现许多科学知识并未应用于常规医学实践。

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02:44 医学对饮食、运动和环境因素的影响关注甚少。

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03:20 饮食模式会显著影响人们感染COVID-19的严重程度。

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04:09 营养对健康的影响是通过食物、营养物质和肠道微生物之间的关系来实现的。

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04:31 我研究了肠道通透性（leaky gut）的概念，即肠道屏障功能的破坏。

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04:58 我是一个转化型临床医生，将基础科学研究应用于我的临床实践。

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05:49 我过去15到20年的研究重点是肠道微生物组及其与新陈代谢、基因和免疫系统的相互作用。

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06:34 肠道微生物组对免疫系统功能有重大影响，因为三分之二的免疫细胞位于小肠内壁。

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07:19 肠道微生物组产生的丁酸盐对表观遗传学有直接影响。

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08:34 丁酸盐是一种组蛋白去乙酰化酶抑制剂，它影响基因表达。

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10:52 普氏梭菌（Tricholobacterium prausnitzii）是主要的丁酸盐生产菌，它喜欢难消化的碳水化合物。

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11:31 丁酸盐生产菌喜欢难消化的碳水化合物，例如抗性淀粉。

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12:23 摄入合适的物质，才能自然吸引并促进有益菌群的生长，但情况比这更复杂。

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13:14 益生菌的菌株非常重要，仅仅补充双歧杆菌和乳酸杆菌可能无效。

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13:56 靶向噬菌体疗法可能是微生物组研究的未来方向。

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14:54 研究微生物组及其病毒的复杂性很高，目前我们对噬菌体疗法的了解还不够。

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15:38 有些益生菌可以改变整个系统的动态，创造空间让其他微生物生长，我称之为“亚历山大菌”。

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17:08 布拉迪酵母菌（Saccharomyces boulardii）和枯草芽孢杆菌（Bacillus subtilis）7092菌株是“亚历山大菌”的例子。

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17:46 枯草芽孢杆菌7092菌株可以创造一个环境，让健康的微生物组重建自身。

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18:37 人们正在研究如何保护益生菌，使其在肠道的特定部位释放。

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19:06 能够通过胃酸的益生菌更可能发挥作用。

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19:39 枯草芽孢杆菌7092菌株的影响主要在结肠。

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20:16 直肠给药的益生菌可能无法逆行到达整个结肠。

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21:24 肠道微生物组会随着时间变化而变化，这与肠道蠕动无关。

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21:53 肠道内存在两种主要的细菌群落：附着在肠壁上的和存在于粪便中的。

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23:00 在进食之前，身体会通过多种途径发出信号，影响肠道功能。

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23:43 胃酸会杀死许多细菌，为其他细菌创造空间。

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24:12 抑制胃酸的药物会对肠道微生物组产生不利影响。

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24:57 胃酸不足也可能导致胃肠问题。

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25:26 对于酸敏感的人，控制症状的方法有很多，并不一定要抑制胃酸。

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26:21 我致力于帮助患者摆脱长期抑制胃酸的药物治疗。

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26:21 我比一些典型的胃肠病学家更开放地接受不同的治疗方案。

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26:46 大多数药物像“生物约束衣”一样，会抑制细胞功能，并产生副作用。

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27:08 40年前，我开始寻找其他帮助人们康复的方法，因为我对我当时拥有的工具感到沮丧。

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28:04 我被认为是功能医学的创始人之一。

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28:34 我是一个受过良好训练的内科医生，我理解医生的思维方式。

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28:52 我现在只做远程医疗。

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D:2025.09.06<markdown>

00:00

Forget frequently asked questions. Common sense, common knowledge, or Google. How about advice from a real genius? 95% of people in any profession are good enough to be qualified and licensed. 5% go above and beyond. They become very good at what they do, but only 0.1%. 语法解析

00:16

Richard Jacobs has made it his life's mission to find them for you. He hunts down and interviews geniuses in every field. Sleep science, cancer, stem cells, ketogenic diets, and more. Here come the geniuses. This is the Finding Genius Podcast with Richard Jacobs. 语法解析

00:37

Hello, this is Richard Jacobs with the Finding Genius Podcast, now part of the Finding Genius Foundation. I have Dr. Leo Garland. He's the author of The Allergy Solution, and he works on gastrointestinal dysregulation, which we'll get into. So welcome, Leo. Thanks for coming. It's great to be talking with you. Well, tell me a bit about your background. What got you into caring about digestion and all the topics you currently… 语法解析

01:03

I've been a practicing internist for a few decades, actually. And early on in my career, I realized there were a lot of problems that were not being solved by the tools I had been given during my training. And so I set out to try and understand what's the nature of these common problems, 语法解析

01:25

for which there are not really satisfactory treatments. There may be treatments that suppress symptoms. They don't really get to the root of the problem. And why is this happening? And are there ways that I can problem solve to come up with 语法解析

01:40

creative and innovative solutions. And so I've been following that path for about 40 years now. And I was particularly interested in three, four factors, I would say, that emerged. And what I did was I would go to the scientific literature. I would read the research literature and then figure out how to apply it in my clinical practice. What was amazing to me was there was so much science. 语法解析

02:09

behind these areas. And yet none of it had really crossed over into the conventional practice in medicine. The areas… What's an example of that? Yeah, well, the areas include nutrition. They include kind of the body-mind connection or mind-body connection. And I actually did some training in behavioral medicine and environmental health. And this has changed dramatically 语法解析

02:32

somewhat over time, but there is still very little attention paid to the impact of diet, patterns of exercise, and environmental factors. 语法解析

02:44

In many conditions, let's just take cardiovascular disease, for example, and heart attacks. You know, they're viewed as this is, I mean, diet has kind of gotten some attention, but very, really limited attention. That's viewed as being a manifestation of blood flow and cholesterol. As I've described in some of my writing, there are environmental influences on the risk. We take COVID-19, for example, which actually affects 语法解析

03:09

This is actually really important research that's been done over during the pandemic, that a person's dietary pattern has a significant impact 语法解析

03:20

on the likelihood that they will get severe COVID versus mild COVID. A study done of healthcare professionals in six countries looking at their diet in the year preceding illness, retrospectively using standardized and validated questionnaires, and then looking at the outcome of COVID. These were all people who had survived. Is it diet you think that's doing it, or is it the resulting microbial process? 语法解析

03:48

It's both. And in terms of the microbiome, I started to realize that a lot of the effects of nutrition on health were mediated through the relationship between food and nutrients and the microbes in your gut. And so… 语法解析

04:09

Going back at least 30 years, I began studying that connection. Before there was a term microbiome that was out there. These were just gut organisms. And I did a lot of work in the concept that came to be called leaky gut, which is not a term that I particularly like, but it refers to a breakdown in the barrier function of the intestinal tract. And so… 语法解析

04:31

You asked me, am I a researcher or am I a clinician? I'm basically a clinician, but I would view myself as a kind of translational clinician. That is, I spend a lot of time looking at basic scientific research and then trying to figure out how to apply that to the patients that I'm seeing in the office. Yeah, that's great. Like you said earlier, a lot of the stuff you were finding, there was no mention of it in clinical practice. So the fact that you look… 语法解析

04:58

Probably sadly means a lot of doctors don't look. And the side that you look will give you new ideas and ways to treat people. And you can correlate, you know, what you're seeing in patients clinically with what the research is saying. So, yeah, that's good that you did that. You know, maybe, I don't know, 25 or 30 years ago, a patient of mine said, well, my gastroenterologist said to me, there's no such thing as a lead deep gut. Well, 10 years after that, there were articles in major medical journals. 语法解析

05:23

the New England Journal of Medicine, using that term, leaky gut. And so there has been, I would say, a lot of the focus of my research in reviewing the scientific literature and then applying it over the past 15 or 20 years has been focused on the gut microbiome, which is the collection of all the microbes that 语法解析

05:49

living in the human GI tract. And with that, I include the mouth, from mouth all the way through. And the interactions between those microbes and our metabolism, our genes, and also at our immune system. And about 语法解析

06:06

Two-thirds of the immune cells that we have are located in the lining of the small intestine, and they don't stay there. They travel from there to various organs. Some of them come from these organs to the small intestine and then go back. It's kind of like this is their school. This is where they get trained. And there's a major impact of the nature of the microbes growing there and the way our immune system works. 语法解析

06:34

Well, the only thing that keeps you alive for 80, 90 years is what you eat, what you drink, what you breathe. But somehow a lot of science says, ah, it's not important until recently, which I find crazy. So undoubtedly diet is a monstrous component or a major component of what happens to us. I wanted to ask you a question. Epigenetically, has anyone studied what happens before and after someone eats a meal? How much epigenetic change is there and 语法解析

07:02

Is there anything to be learned from that? Oh, there's a lot to be learned from it. I don't know if that's been studied exactly the way you asked the question, like before and after a meal, especially in humans, but one of the most important substances produced 语法解析

07:19

by the gut microbiome is a volatile short-chain fatty acid called butyrate or butyric acid. Now, volatile means that it evaporates, goes right through membranes. It's a fatty acid, so it's something that's soluble in fat. And the short chain means it's very small. It actually has only four carbon atoms in it, which is what makes it volatile. So butyrate is produced in the large intestine 语法解析

07:48

by the activity of a number of different types of bacteria that are present, and most of these are considered beneficial bacteria. In the large intestine, butyrate acts, first of all, to nourish the cells that line the large intestine. About 70% of the energy generated there to support cellular life comes from the oxidation of the butyrate. 语法解析

08:14

It also has anti-inflammatory effects and anti-cancer effects, and it helps the repair of down in cells. Now, that butyrate is absorbed into the body, and it travels throughout your body. It even gets into your brain. One of the effects of butyrate is a direct effect on epigenetics. 语法解析

08:34

And this term is a little complicated, but butyrate is what is called a histone deacetylase inhibitor. Now, histones are proteins that surround the DNA in your cells. 语法解析

08:47

And they regulate the way DNA expresses itself because your genes are, most of your genes are silent much of the time and then they get activated. Acetylation is a way of activating genes. Deacetylation, it activates genes. 语法解析

09:03

And I mean, this is a triple negative, maybe, but the butyrate inhibits the deacetylation. So in the case of brain injury, and this has been studied quite thoroughly in laboratories, in the case of brain injury, butyrate enhances the repair of the brain and the recovery by allowing genes to 语法解析

09:26

that are involved in brain repair and recovery to get turned on. And I would say that's probably the most studied direct link between the gut microbiome and epigenetics. 语法解析

09:40

Before we continue, I've been personally funding the Finding Genius podcast for four and a half years now, which has led to 2,700 plus interviews of clinicians, researchers, scientists, CEOs, and other amazing people who are working to advance science and improve our lives and our world. Even though this podcast gets 100,000 plus downloads a month, we need your help to reach hundreds of thousands more worldwide. 语法解析

10:02

Please visit findinggeniuspodcast.com and click on support us. We have three levels of membership from $10 to $49 a month, including perks such as the ability to see ahead in our interview calendar and ask questions of upcoming guests, transcripts of podcasts you're interested in, the ability to request specific topics or guests, and more. Visit findinggeniuspodcast.com and click support us today. Now back to the show. 语法解析

10:27

So which bacteria are the most efficient or best producers of uterates, and then what are their favorite foods? Well, there are a number of them. Probably the main one is not available as a probiotic, and its name is a little, would be hard for most people to learn. It's called Tricholobacterium prausnitzii. And this is what's called a keystone species in that its presence and its activity supports 语法解析

10:52

a lot of the activity of bacterial communities in the gut. Just as a keystone holds an arch together, keystone species hold bacterial communities together. And butyrate supports the growth of bifidobacteria, which most people know about because that is available as probiotics. And there's a 语法解析

11:15

reciprocal and synergistic relationship between fecal bacterium prosonancy and bifidobacteria. Now, generally, what F-prosonancy likes and the other butyrate producers like are poorly digested carbohydrates. 语法解析

11:31

That is, sugar doesn't do them any good. You just digest and absorb that. But the more complex sugars that are not readily absorbed are, they get down to where the bacteria are, and then they feed those bacteria. So resistant starch, which is found in a number of starchy vegetables, that F-prosonancy really likes that and those kinds of foods. 语法解析

11:56

High fiber, high fiber diets, basically. How much do the, you know, people are trying to take probiotics to actively seed their guts, but it seems like the best way is, you know, like if you build it, they will come. Instead, if you feed it, they will come. So if you have the right materials that are released in the right part of the digestive tract, it should naturally attract and help grow the community of the right bacteria that you want. Well, it may work on… I just made up. 语法解析

12:23

It may work that way, but the situation is more complicated than that because sometimes what you're feeding the bacteria that you want to be active may also feed bacteria that you don't want to be active. And even though there is this concept that prebiotics can feed, you can direct prebiotic foods and 语法解析

12:47

and bacterial species that you want to grow. It's not that simple. And as far as taking probiotics goes, there are a couple of issues with probiotics. One is that the strain of the probiotic is very important. It's not just the species. So probiotic bacteria are characterized in several ways, the way that all living organisms are. 语法解析

13:14

where most living organisms. Generally, there's a genus like Lactobacillus or Bifidobacterium, and then there's a species like it could be Acidophilus or Bifidobacterium infantis. 语法解析

13:27

That's not enough. The specific strain within that species, different strains can have different effects. And merely putting in bifidobacteria and lactobacilli, they may not even grow. I see that very often. They just can't get into the niche you're putting them in, but they're not metabolically active. So sometimes you have to create space for them. There are some… 语法解析

13:52

Besides broad-spectrum antibiotics, what if you had a phage 语法解析

13:56

that particularly target, let's say you have like Clostridium difficile, I can't even pronounce it right. But let's say you had that. C. diff, we'll just call it C. diff. Yeah, C. diff. What if you found a phage that naturally predates on C. diff? You took that along with prebiotic and probiotic to give, you know, a helping hand to the new species that you'd rather have there than from when C. diff took over. Bacteriophages might be the future of microbiome work. 语法解析

14:26

There are about 30 times as many bacteriophages or viruses that basically go into the bacteria. Now, some of them, the name bacteriophage means it eats bacteria. Some of them do eat the bacteria, that is, they kill the bacteria. But some of them live with the bacteria and learn to change bacterial function. And it's even possible that the bacteria are finding ways to change the activity of the phages. 语法解析

14:54

I mean, that's so the level of complexity, looking at the microbiome on its own without the viruses, the bacteriophages is like rocket science meets quantum physics. The level of complexity that's introduced when you start looking at the effect of these viruses on the whole, on the structure and function of these multiple communities in your gut, that's 语法解析

15:18

We don't have enough information to know what to do. But I do think that targeted phages, phage therapeutics, are part of the future of medicine. But we're not there. We're not quite there yet. Now, the… Oh, so one place where we are is we have probiotics. Now, there are some probiotics 语法解析

15:38

They come into the system and they really alter the dynamics of the whole system. And they create space for other organisms, not just themselves. I call these, I coined the term for this Alexander organisms, Alexander the Great, you 语法解析

15:57

you know, conquered much as the known world at the time, but he didn't do it. I mean, he was just the general whose troops did. He, of course, he couldn't have done it without them, without the Macedonian army, but they were unlikely to have done it without him. So it was his leadership and his skills that, 语法解析

16:16

that enable that to happen. Well, there are probiotics that have that characteristic. They don't actually take over the whole gut, but they start to create changes that then enable other changes that are really significant in terms of overall function. And these have been studied in different situations and 语法解析

16:40

And a couple of them may be commercially available. There's a yeast called Saccharomyces boulardii that was discovered in what is now Vietnam about 100 years ago and was developed into a probiotic. There's this extraordinary Russian or Russian and Ukrainian probiotic, which is a strain of Bacillus subtilis. It's Bacillus subtilis 7092. And this is an example of where strains matter. Bacillus subtilis 7092. 语法解析

17:08

is a soil-derived organism. It forms spores. It lives in the soil. If you eat raw food, you're going to get some Bacillus subtilis. Bacillus subtilis and its relatives have multiple beneficial effects in the body, not because they set up shot and become part of your normal bacteria the way that Bifidobacterium and related species do, but because 语法解析

17:34

They create an environment in which a healthy and productive microbiome can reconstitute itself when it's been disrupted. And of course, all of us have disrupted microbiomes. 语法解析

17:46

So, the Bacillus subtilis 7092 strain has a number of unique effects and it creates the environment in which healthy organisms can grow. So, that's my concept of Alexander organisms. Gotcha. Is there anyone that's making a formulation to protect a given set of strains so that they'll only be released? 语法解析

18:12

in the small intestine or the large intestine or the stomach or, you know, how important and critical is placement of a probiotic, you know, inbound strains in the right area. So it's protected from, again, stomach acid, but it's also protected maybe from competing bacteria that would out-compete it if it's exposed too early. That's a very good point. And there are people working on that. The first… 语法解析

18:37

danger to probiotics that you take is stomach acid. And so organisms that are able to get past stomach acid, they're more likely to be able to function as Alexander organisms. That's one of the strong points of both the Saccharomyces lewardi and especially the Bacillus subtilis, because Bacillus subtilis is a spore-forming organism. If you take it, it has a protective coating around it. 语法解析

19:06

You don't need to refrigerate it. It doesn't matter whether you take it with or without food. By the time it gets through this, after it gets through the stomach and somewhere in the small intestine, that spore gets digested and removed. 语法解析

19:19

And then the free-living bacteria are able to start working. The 7092 allegedly is designed to have most of its impact in the large intestine and the colon. But I can't say that I've reviewed enough of it. I haven't seen enough of the research in English to be certain of that. 语法解析

19:39

Well, for organisms that take up, you know, that are predominant in the colon, why not do probiotics depository? Well, you could do it that way. It's certainly more annoying than swallowing a pill. Right, but if that is… 语法解析

19:53

Part to get to would be large intestine and especially small intestine. But if something hangs out in the colon in predominance, then why not avoid all those stomach gases and the whole digestive system go bloop? Well, the one issue there is just as you put something into the rectum with a suppository, it doesn't mean that it's going to travel retrograde throughout the colon because it's 语法解析

20:16

The whole direction of flow is from top to bottom. So if you put something in at the bottom, it's got a lot of work to do to try and move up. I see what you mean, yeah. Whereas if you take it orally, and especially if it's an organism like the Bacillus subtilis 7092 that has no problem getting stomach acid and gets released – 语法解析

20:38

somewhere in the small intestine where there's very little competition for it. By the time it gets down to the, it gets, it will travel through the whole colon. Interesting. And also, I mean, this is gross, but the condition of the colon, especially the sigmoid colon, changes dramatically whether it's full or empty. Has anyone studied the bacterial dynamics when it's full versus when it's empty and how that changes as we go through the cycle of, you know, stool formation and then evacuation? 语法解析

21:07

That has been looked at. Again, I don't think the question has been approached exactly the way that you framed it. But there are changes in the microbiome that are related to time of day, independent of gut motility. That is… 语法解析

21:24

Just as we have a diurnal cycle, there are bacteria that are sensitive to our body's diurnal rhythm, and they become more or less active at different times of day. And then it's also important to understand that there are two super communities of bacteria. They're the ones that are adherent to the large intestine, to the lining cells, and there are those that appear in the stool. 语法解析

21:53

What appears in the stool is not necessarily representative of what's attached to the lining. And because some of those cells that attach to the lining, they like it there. You know, they don't particularly want to get shed. So that's an example of the kinds of very complex dynamics that can occur. Yeah. Yeah, that's crazy. I didn't realize that. Yeah. 语法解析

22:15

Very interesting. Yeah, it is very challenging. But over the past decade, it has started to – I've been so gratified to see the way in which this area that was kind of considered a little odd and out there when I started working with it has really moved into the mainstream. 语法解析

22:35

Has anyone looked at the signaling that may be occurring? I'm looking at a hamburger, I'm going to eat it, and I start salivating. What do the bacteria in my mouth know from that? Or I start to eat a hamburger or whatever. Is it signaling my gut bacteria? XYZ is coming. Is there any quick signaling that beats the progression of the food to let my body know what's coming? 语法解析

23:00

Yeah, the signaling occurs on a whole lot of levels. First of all, you start – like you smell something that smells good and you start feeling hungry. There are changes that occur in your brain that impact the function of your gut. And even – I mean this was – 语法解析

23:20

This was studied over 100 years ago, even before they knew anything about the gut microbiome. You know, you start to salivate. The saliva changes the composition of the oral microbiome, but you also start to produce stomach acid when you, you know, your appetite is wet and you're preparing to eat. Well, the stomach acid kills a lot of organisms in the stomach. It also drips down into the 语法解析

23:43

small intestine where it stimulates the pancreas to start secreting juices. The acid that gets into the small intestine is also antibacterial. It's wiping out a lot of the local bacteria, but then there's a lot that makes room for the bacteria that are coming down from your mouth and from the food. And there's a widespread use of acid suppressive drugs because of problems like heartburn. And those drugs have a significant impact and not a favorable impact. 语法解析

24:12

Well, the proton inhibitors. Right, right. And H2 blockers. They really impact the composition of the gut microbiome and they increase the risk of foodborne infection and of C. difficile, C. diff colitis acting on. 语法解析

24:30

Yeah, so gastroenterologists have said to patients of mine, oh, you can take this forever. There's no side effects, there's no problems. I mean, the research literature does not bear that out. Just so you know, I don't know if this will be helpful to you, but from what I've experienced directly, it's actually you don't have enough stomach acid that can cause a lot of these gastrointestinal problems. So taking, like one supplement I take is called HCL. It has betaine, pepsin, 语法解析

24:57

etc. It's a nice formulation by biotics and that works much better than anything to lower the acid. Usually it's the opposite is what I found works better. Well, I have a lot of patients for whom that's the case, in whom acid suppression does not even help them symptomatically. They need more acid. Sometimes that'll come from the betaine hydrochloride. Sometimes it will come from herbal products that stimulate acid secretion. But in those people who are acid sensitive, 语法解析

25:26

There are much better ways to control symptoms than with acid suppression. Yeah, I'm sure. I put out an e-book called The Heartburn and Indigestion Solution. It looked at that, I don't know, maybe a number of years ago. I don't remember how many. Well, it's real. They have worked. I mean, when I see a patient who's on chronic acid suppression, my number one goal is to help them get off it. I can succeed with that about 95% of the time. 语法解析

25:55

Oh, that's really good. I mean, you know, and I'm not going to say most gastroenterologists are, you know, not helpful. But again, you definitely seem to be a lot more open to different protocols and things than some typical ones that I've spoken to. So that's excellent for you. It's good. Well, you know, one of the problems with the physician's encounter is they're trained in a particular way of thinking about treating illness. 语法解析

26:21

And that most of the drugs that we have sort of work like biological straitjackets. That is, they are designed to prevent some cellular function that's hyperactive from getting out of control. Well, I mean, but the problem is that these cellular functions have a purpose. And so almost all of the side effects of drugs 语法解析

26:46

are directly related to what their therapeutic intent is. So if all the tools that you have in front of you are tools that suppress specific cell functions, you're going to be limited in what you're able to accomplish. That was one of the big frustrations for me 40 years ago when I started to look for other ways of trying to help people get better. 语法解析

27:08

You know, like you, and so you're treating someone for arthritis. Well, the drugs that you use to treat them for arthritis are, they're going to create gastrointestinal problems. They could cause ulcers. They may also cause kidney problems. And you start, your blood pressure goes up. If you can find a nutritional approach to deal with arthritis, if someone has an ulcer or esophagitis or 语法解析

27:31

Yeah, that's fantastic. 语法解析

27:53

So why wouldn't you call yourself a functional gastroenterologist? Because it sounds like that's what you are. Oh, well, I am considered one of the founders of functional medicine. Oh, wow. That's awesome. 语法解析

28:04

Thank God for you. I appreciate that, that you're one of the originators of it. That's really great. Yeah, some of the concepts that I started presenting 30 years ago became sort of foundational for the functional medicine approach. But in terms of the world at large, I am a board-certified internist. I was trained, very well trained in internal medicine, and I understand the way that doctors think and why they think that. 语法解析

28:34

Okay. Well, very good. Leo, how can people find you if you need to be found, you know, for clinical help? They got to go to the doctor, gastroenterologist or internist. Where do you practice and work? You know, I don't know if you do telemedicine or you'll got to come in. Right. Well, these days I'm doing telemedicine only. I'm located in New York. I, 语法解析

28:52

I have very limited capacity for new patients, but I am interested in helping people with complex chronic problems get the help that they need. I have a website, drgalland.com. It's G-A-L-L-A-N-D.com. 语法解析

29:10

That's correct. Dr. D-R-G-A-L-L-A-N-D dot com. And there are links there to various publications and presentations that I've given. On the landing page, there's an article called Long COVID Prevention and Treatment. And for the past three years, a lot of my focus has been on helping people understand and overcome the challenges of the pandemic. 语法解析

29:33

And even though the pandemic may be over, but endemic COVID is quite dangerous and long COVID may be the major public health impact of the endemic. Okay, well, very good. Leo, thank you so much for coming on the podcast. I really appreciate it. Okay, well, great. Great to talk with you. If you like this podcast, please click the link in the description to subscribe and review us on iTunes. You've been listening to the Finding Genius Podcast with Richard Jacobs. 语法解析

30:05

If you like what you hear, be sure to review and subscribe to the Finding Genius Podcast on iTunes or wherever you listen to podcasts. And want to be smarter than everybody else? Become a premium member at FindingGeniusPodcast.com. This podcast is for information only. No advice of any kind is being given. Any action you take or don't take as a result of listening is your sole responsibility. Consult professionals when advice is needed. 语法解析

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利奥・加兰博士（Dr. Leo Garland）是《过敏解决方案》（The Allergy Solution）一书的作者，主要研究胃肠道功能失调。

加兰博士已从事内科临床工作数十年。在职业生涯早期，他发现自己接受医学培训时学到的方法，无法解决许多常见的健康问题。于是，他开始尝试探究这些问题的本质 —— 那些尚无满意治疗方案的病症，现有疗法往往只能缓解症状，无法根除病因。他想弄清楚背后的原因，并寻找具有创新性的解决方案，这一探索之路已持续约 40 年。

在研究过程中，加兰博士特别关注到三四个关键领域。他会查阅科学文献，研读研究成果，再思考如何将其应用到临床实践中。令他惊讶的是，这些领域背后有大量科学依据支撑，却几乎未被纳入传统医学实践。这些领域包括营养学、身心关联（或心身关联），他还接受过行为医学和环境健康方面的培训。尽管随着时间推移，情况有所变化，但目前医学对饮食、运动模式和环境因素的影响仍关注甚少。

以心血管疾病（如心脏病发作）为例，饮食虽得到一定关注，但程度非常有限，这类疾病通常被认为与血液流动和胆固醇相关。而加兰博士在著作中提到，环境因素会影响患病风险。以新冠为例，疫情期间的重要研究表明，一个人的饮食模式对其感染新冠后症状的严重程度有显著影响 —— 是发展为重症还是轻症，与饮食密切相关。

有一项针对六个国家医疗专业人员的研究，通过标准化且经验证的问卷，回顾性调查了他们在患病前一年的饮食情况，并观察其新冠感染后的结局（所有研究对象均已康复）。当被问及是饮食本身还是由此产生的微生物过程在起作用时，加兰博士表示两者皆有影响。他进一步指出，早在 “微生物组” 这一术语出现之前，自己就开始研究营养对健康的影响，而这种影响很大程度上是通过食物、营养物质与肠道微生物之间的关系介导的，当时他研究的对象还只是被称为 “肠道微生物”。

加兰博士在 “肠道通透性”（肠漏 leaky gut，他本人并不特别喜欢这一术语，但指的是肠道屏障功能的破坏）领域做了大量研究。他认为自己本质上是一名临床医生，但更倾向于将自己定义为 “转化型临床医生”—— 花大量时间研究基础科学研究，再尝试将其应用到门诊患者的治疗中。

他提到，遗憾的是，许多医生并不会主动去关注这些研究成果，而主动探索能带来治疗新思路，还能将临床观察到的患者情况与研究结论相互印证。例如，大约 25 到 30 年前，他的一位患者表示，胃肠科医生称 “不存在肠道通透性问题”，但 10 年后，《新英格兰医学杂志》等主流医学期刊开始使用 “肠道通透性” 这一术语。

过去 15 到 20 年，加兰博士研究和文献综述的重点一直放在肠道微生物组（即生活在人体胃肠道内所有微生物的集合，包括从口腔到肠道末端的整个消化道），以及这些微生物与人体新陈代谢、基因和免疫系统之间的相互作用。人体三分之二的免疫细胞位于小肠内壁，这些细胞并非固定不动，会往返于小肠和其他器官之间，小肠就像它们的 “训练学校”，肠道内微生物的种类和状态对免疫系统的运作方式有重要影响。

加兰博士认为，支撑人存活 80 到 90 年的关键因素是饮食、饮水和呼吸，但直到最近，许多科学研究才开始重视这些因素，这在他看来有些不可思议，饮食无疑是影响人体健康的重要组成部分。

当被问及是否有研究关注人进食前后的表观遗传变化，以及能从中获得什么启示时，加兰博士表示，虽不确定是否有研究完全按照 “进食前后” 的视角展开（尤其是在人体研究中），但肠道微生物产生的一种物质 —— 挥发性短链脂肪酸（丁酸，butyrate 或 butyric acid），与表观遗传学有直接关联。丁酸具有挥发性（可蒸发并穿透细胞膜）、脂溶性，且分子结构小（仅含 4 个碳原子），由大肠内多种有益细菌活动产生。

在大肠中，丁酸首先为大肠内壁细胞提供营养 —— 大肠细胞维持生命所需能量的 70% 来自丁酸的氧化；其次，丁酸还具有抗炎、抗癌作用，并有助于细胞修复。此外，丁酸会被吸收到体内，随血液循环到达全身，甚至能进入大脑，其重要作用之一就是对表观遗传学产生直接影响。

丁酸被称为 “组蛋白去乙酰化酶抑制剂”。组蛋白是细胞内包裹 DNA 的蛋白质，负责调控 DNA 的表达（人体大多数基因大部分时间处于沉默状态，需被激活后才发挥作用）。乙酰化是激活基因的一种方式，而去乙酰化则会抑制基因激活，而丁酸通过抑制去乙酰化过程，间接促进基因激活。例如，在脑损伤研究中（实验室研究已较为深入），丁酸能通过激活参与脑修复和恢复的基因，促进大脑修复与康复，这也是目前研究最多的肠道微生物组与表观遗传学之间的直接关联。

当被问及哪些细菌是最高效的丁酸盐产生菌，以及它们偏好的食物时，加兰博士指出，主要的丁酸盐产生菌之一是普氏梭菌（Tricholobacterium prausnitzii），这种细菌目前无法作为益生菌获取，且名称对普通人来说较难记忆。它属于 “关键物种”，其存在和活动能支撑肠道内细菌群落的大量活动，就像拱顶石支撑拱门一样，关键物种支撑着整个细菌群落的稳定。同时，丁酸盐还能促进双歧杆菌（一种常见于益生菌中的细菌）的生长，普氏梭菌与双歧杆菌之间存在相互促进的协同关系。

总体而言，普氏梭菌及其他丁酸盐产生菌偏好的是难消化的碳水化合物。普通糖类会被人体直接消化吸收，无法为这些细菌提供营养；而结构更复杂、不易被人体吸收的糖类，能到达肠道细菌所在的部位，成为细菌的 “食物”。例如，抗性淀粉（存在于多种淀粉类蔬菜中）就是普氏梭菌等细菌喜爱的食物，高纤维饮食也能为这类细菌提供适宜的营养。

对于人们通过服用益生菌来 “培育” 肠道菌群的做法，加兰博士认为，更有效的方式或许是 “提供适宜的营养，有益菌群自然会生长”（即 “feed it, they will come”）—— 若能在消化道合适部位提供合适物质，就能自然吸引并促进所需有益菌群的生长。但实际情况更为复杂，因为为目标菌群提供的营养，有时也可能被有害菌群利用；且尽管有 “益生元可定向促进特定菌群生长” 的概念，但实际操作并非如此简单。

在益生菌方面，存在两个关键问题：一是菌株至关重要，不能仅关注菌种。益生菌细菌的分类与所有生物类似，有属（如乳杆菌属 Lactobacillus、双歧杆菌属 Bifidobacterium）、种（如嗜酸乳杆菌 Acidophilus、婴儿双歧杆菌 Bifidobacterium infantis），但仅知道属和种还不够，同一种类下的不同菌株可能产生不同效果。二是单纯补充双歧杆菌和乳杆菌，这些细菌可能无法在肠道内生长 —— 加兰博士在临床中经常观察到这种情况，这些细菌无法在肠道内找到合适的 “生态位”，也无法进行代谢活动，因此有时需要为它们 “创造生存空间”。

除了广谱抗生素，靶向噬菌体疗法可能是微生物组研究的未来方向。例如，针对艰难梭菌（C. diff），若能找到天然以其为食的噬菌体，将其与益生元、益生菌配合使用，就能帮助有益菌群在肠道内占据优势，替代艰难梭菌。肠道内的噬菌体数量约为细菌的 30 倍，部分噬菌体会杀死细菌（“bacteriophage” 字面意思即 “食菌者”），部分则与细菌共生并改变细菌功能，甚至细菌也可能通过某种方式改变噬菌体的活动。

研究肠道微生物组本身已如同 “火箭科学与量子物理的结合” 般复杂，若再加入噬菌体对肠道菌群结构和功能的影响，复杂度会更高，目前人类对此的了解还远远不足。但加兰博士坚信，靶向噬菌体疗法将是未来医学的一部分，只是目前尚未达到成熟应用阶段。

加兰博士提出了 “亚历山大菌”（Alexander organisms）的概念 —— 有些益生菌进入人体后，能改变整个肠道系统的动态平衡，不仅自身能生存，还能为其他有益菌群创造生存空间，这一命名灵感来源于亚历山大大帝（Alexander the Great）—— 他虽征服了当时已知的大部分世界，但离不开马其顿军队的支持，而军队也需要他的领导与策略，二者相互依存。这类益生菌不会完全占据肠道，而是通过引发一系列变化，对肠道整体功能产生重大积极影响，且已在不同场景中得到研究，部分已实现商业化应用。

例如，布拉迪酵母菌（Saccharomyces boulardii）是约 100 年前在现越南地区发现的一种酵母菌，现已被开发为益生菌；另一种是俄罗斯及乌克兰研发的枯草芽孢杆菌（Bacillus subtilis）7092 菌株，这一案例也体现了菌株的重要性。枯草芽孢杆菌 7092 源自土壤，能形成孢子，若食用生食，人体可能会摄入少量枯草芽孢杆菌及其近缘菌种。这类细菌能为人体带来多种益处，但其作用方式与双歧杆菌不同 —— 它们不会在肠道内定居并成为正常菌群的一部分，而是在肠道被破坏时，创造一个适宜健康、活跃微生物组重建的环境。而事实上，几乎所有人的肠道微生物组都存在不同程度的破坏。

当被问及是否有研究通过特定配方保护益生菌菌株，使其仅在小肠、大肠或胃等特定部位释放，以及益生菌在消化道中释放位置的重要性时，加兰博士表示，这是一个非常关键的问题，已有研究人员在开展相关工作。益生菌进入人体后面临的首要威胁是胃酸，因此能通过胃酸的益生菌，更有可能发挥 “亚历山大菌” 的作用 —— 布拉迪酵母菌，尤其是枯草芽孢杆菌（能形成孢子，孢子外有保护壳），就具备这样的优势：无需冷藏，与食物同服或空腹服用均可；经过胃部后，孢子外壳在小肠某处被消化分解，释放出活菌并开始发挥作用。

据称，枯草芽孢杆菌 7092 菌株的主要作用部位是大肠（结肠），但加兰博士表示，由于未查阅到足够多的英文研究文献，无法完全确认这一点。对于 “通过栓剂将益生菌直接输送到结肠” 的想法，加兰博士认为，这种方式虽能避开胃部消化，但存在一个问题：肠道内容物的流动方向是 “从上到下”，直接从直肠送入的益生菌难以逆行到达整个结肠；而口服益生菌（如枯草芽孢杆菌 7092）能顺利通过胃酸，在小肠某处释放（此处竞争较少），随后随肠道蠕动到达整个结肠，覆盖范围更广。

此外，结肠（尤其是乙状结肠）的状态会随内容物充盈或排空发生显著变化。虽暂无研究完全按照 “结肠充盈与排空时细菌动态变化” 的视角展开，但已有研究发现，肠道微生物组会随一天中的时间变化（与肠道蠕动无关）—— 就像人体有昼夜节律一样，部分细菌对人体昼夜节律敏感，在一天中不同时间段活跃度不同。同时，肠道内存在两种主要的细菌群落：一种附着在大肠内壁细胞上，另一种存在于粪便中，而粪便中的菌群并不一定能代表附着在肠壁上的菌群，因为部分肠壁附着菌更倾向于留在原位，不愿被排出体外，这也体现了肠道菌群动态变化的复杂性。

加兰博士表示，过去十年中，令他深感欣慰的是，当他刚开始研究肠道微生物组时，这一领域还被认为 “小众且边缘化”，如今已逐渐进入主流视野。

当被问及 “看到汉堡准备进食时开始分泌唾液，口腔细菌是否能感知这一信号？进食前是否有快速信号提前告知肠道细菌‘即将摄入某种食物’” 时，加兰博士指出，这类信号的传递涉及多个层面。首先，当人闻到美食香味、产生饥饿感时，大脑会发生变化，进而影响肠道功能 —— 这一现象早在 100 多年前（人们对肠道微生物组尚无认知时）就已被研究。例如，唾液分泌会改变口腔微生物组的构成；当人产生食欲、准备进食时，胃部会开始分泌胃酸，胃酸不仅能杀死胃内大量细菌，还会流入小肠，刺激胰腺分泌消化液，同时小肠内的胃酸也具有抗菌作用，会清除部分本地细菌，为口腔及食物中的细菌 “腾出空间”。

目前，由于胃灼热等问题，抑制胃酸的药物（如质子泵抑制剂、H2 受体阻滞剂）被广泛使用，但这类药物会对肠道微生物组构成显著不利影响，改变菌群构成，增加食源性感染及艰难梭菌结肠炎（C. diff colitis）的患病风险。加兰博士提到，部分胃肠科医生会告知患者 “这类药物可长期服用，无副作用”，但研究文献并不支持这一说法。他通过临床经验发现，胃酸不足也可能导致多种胃肠道问题，因此部分患者服用盐酸甜菜碱（HCL）、胃蛋白酶等补充剂（如 Biotics 公司的相关配方），比服用抑酸药效果更好；对于胃酸分泌不足的患者，除补充剂外，也可通过草药产品刺激胃酸分泌；而对于酸敏感患者，有多种比抑酸药更有效的症状控制方法。

加兰博士还曾撰写一本名为《胃灼热与消化不良解决方案》（The Heartburn and Indigestion Solution）的电子书，探讨相关问题。在临床实践中，他将 “帮助长期服用抑酸药的患者停药” 作为首要目标，且成功率约为 95%。

加兰博士认为，医生诊疗过程中存在一个问题：他们接受的训练使其形成了特定的疾病治疗思维，而现有大部分药物的作用方式类似 “生物约束衣”（biological straitjackets）—— 旨在抑制过度活跃的细胞功能，防止其失控。但这些细胞功能本身具有重要生理意义，因此药物的副作用往往与其治疗目的直接相关。若医生仅依赖 “抑制细胞功能” 的工具，治疗效果会受到很大限制。这也是他 40 年前开始寻找其他治疗方法的重要原因 —— 例如，治疗关节炎的药物可能引发胃肠道问题（如溃疡）、肾脏问题，还可能导致血压升高，而通过营养疗法治疗关节炎、溃疡或食管炎等疾病，往往能取得更好的效果。

当被问及为何不称自己为 “功能胃肠病学家” 时，加兰博士表示，他被认为是功能医学的创始人之一。30 年前，他提出的部分概念成为功能医学方法的基础；从职业身份来看，他是一名获得认证的内科医生，接受过系统的内科培训，理解传统医生的思维方式及其形成原因。

当被问及患者如何获取他的临床帮助（如是否提供远程医疗、办公地点等）时，加兰博士表示，目前他仅提供远程医疗服务，办公地点位于纽约，接收新患者的名额非常有限，但他希望能帮助患有复杂慢性疾病的患者获得所需治疗。

听众可通过他的个人网站drgalland.com了解更多信息，网站上有他的各类出版物、演讲内容的链接，首页还有一篇题为《长新冠的预防与治疗》的文章。过去三年，他的主要研究重点是帮助人们了解并应对新冠带来的挑战；尽管疫情大流行阶段可能已结束，但新冠地方性流行仍具有危险性，长新冠症状可能成为地方性流行阶段主要的公共卫生问题。

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D:2025.09.06

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